This is a proposal to study the biosynthesis of TRH in vitro. Its specific concerns relate to the study of biochemical mechanisms of C terminal amidation and N terminal blockade of physiologically active neuropeptides. The overall goal of this research is to not only define possible mechanisms for the post translational cellular processing of small neuropeptides, but more specifically, to elucidate the synthetic pathways for TRH. The relevance of this research to the area of neurobiology is that findings will be broadly applicable to understanding the mechanisms for the cellular storage, synthesis, and secretion of neuropeptides and allow the development of pharmacological agents to inhibit or augment these processes. The relevance of this research to the field of mental health in general is two-fold. First, understanding of the basic mechanisms of neuropeptide synaptic transmission will make it possible to develop pharmacological agents of inhibiting or augmenting these processes, the further development of which may lead to clinically relevant drugs for the modification of abnormal behavior patterns. Secondly, basic understanding of neuronal processes and of possible mechanisms for alteration of normal synaptic transmission should rapidly advance our understanding of the biology of normal and abnormal behavior.